881A Poster - 14. Neural circuits and behavior
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
Shashank Shekhar; Andrew T Moehlman; Minh-Nguyet Hoang; Charles Tracy; Helmut Krämer

Affiliation: UT Southwestern Medical Center

Keywords:
e. synaptic function and organization; f. autophagy

Abstract:
Homeostatic responses are essential for neuronal circuits to adapt to changes in the environment. To investigate the molecular mechanisms controlling homeostatic responses in neurons we use a reversible in-vivo model [1]. Extended exposure to ambient light triggers homeostatic responses including reduced rhabdomere size and loss of synaptic active zones in Drosophila photoreceptor neurons. These responses are reversible and therefore offer an excellent opportunity to study signaling events controlling neuronal homeostatic responses. Here, we identify allnighter (aln) as a novel gene required for the regulation of these responses. aln encodes a secreted pseudokinase that is functionally conserved in humans. Flies mutant for aln have normal visual responses when maintained under a regular 12h:12h light:dark cycle (LD), but lose photoreceptor structural integrity and postsynaptic responses after prolonged exposure to ambient light. This response is transient, and photoreceptors recover when returned to LD. Phenotypes are rescued by expression of Aln or its human homolog, the divergent protein kinase FAM69C, independent of its kinase activity. Aln is expressed in many neurons but, surprisingly, not in photoreceptors. Instead, it is secreted by lamina neurons, most prominently L4, and retrogradely regulates photoreceptor responses including UPR and autophagy, two key pathways of homeostatic responses. Perturbation of photoreceptor output by expression of Shi^ts1 or Tetanus Toxin light chain drastically decreased Aln expression in L4 lamina neurons, and other brain regions. This suggests that the Aln is part of feedback loop in the Drosophila visual system. Aln homologs are highly expressed in mammalian brains suggesting important yet to be discovered functions of these molecules in the mammalian brain.
1. Moehlman, A.T., Casey, A.K., Servage, K., Orth, K., and Krämer, H. (2018). Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration. eLife 7, pii: e38752.